chr3-42658395-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_145166.4(ZBTB47):​c.40C>G​(p.Leu14Val) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Consequence

ZBTB47
NM_145166.4 missense

Scores

6
7
6

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.15
Variant links:
Genes affected
ZBTB47 (HGNC:26955): (zinc finger and BTB domain containing 47) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ZBTB47NM_145166.4 linkc.40C>G p.Leu14Val missense_variant Exon 2 of 6 ENST00000232974.11 NP_660149.2 Q9UFB7-1
ZBTB47NM_001410746.1 linkc.124C>G p.Leu42Val missense_variant Exon 2 of 6 NP_001397675.1
ZBTB47XM_047449234.1 linkc.220C>G p.Leu74Val missense_variant Exon 3 of 7 XP_047305190.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ZBTB47ENST00000232974.11 linkc.40C>G p.Leu14Val missense_variant Exon 2 of 6 5 NM_145166.4 ENSP00000232974.6 Q9UFB7-1
ZBTB47ENST00000680014.1 linkc.124C>G p.Leu42Val missense_variant Exon 2 of 6 ENSP00000504903.1 A0A7P0T820

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
32
GnomAD4 genome
Cov.:
33

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Mar 13, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.40C>G (p.L14V) alteration is located in exon 2 (coding exon 1) of the ZBTB47 gene. This alteration results from a C to G substitution at nucleotide position 40, causing the leucine (L) at amino acid position 14 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.29
BayesDel_addAF
Uncertain
0.033
T
BayesDel_noAF
Benign
-0.19
CADD
Uncertain
26
DANN
Uncertain
1.0
DEOGEN2
Benign
0.32
T
Eigen
Pathogenic
0.90
Eigen_PC
Pathogenic
0.79
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Benign
0.78
T
M_CAP
Uncertain
0.22
D
MetaRNN
Uncertain
0.74
D
MetaSVM
Uncertain
0.65
D
MutationAssessor
Pathogenic
3.2
M
PrimateAI
Uncertain
0.78
T
PROVEAN
Benign
-1.6
N
REVEL
Uncertain
0.58
Sift
Pathogenic
0.0
D
Sift4G
Pathogenic
0.0
D
Vest4
0.63
MutPred
0.60
Loss of sheet (P = 0.0011);
MVP
0.74
MPC
1.2
ClinPred
0.96
D
GERP RS
4.7
Varity_R
0.47
gMVP
0.86

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-42699887; API